Extending the Electron Spin Coherence Time of Atomic Hydrogen by Dynamical Decoupling

We study the electron spin decoherence of encapsulated atomic hydrogen in octasilsesquioxane cages induced by the 1H and 29Si nuclear spin bath. By applying the Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence we significantly suppress the low-frequency noise due to nuclear spin flip-flops up to the point where a maximum T2 = 56 us is observed. Moreover, dynamical decoupling with the CPMG sequence reveals the existence of two sources of high-frequency noise: first, a fluctuating magnetic field with the proton Larmor frequency, equivalent to classical magnetic field noise imposed by the 1H nuclear spins of the cage organic substituents, and second, decoherence due to entanglement between the electron and the inner 29Si nuclear spin of the cage

A Snapshot of photoresponsive liposomes in cancer chemotherapy and immunotherapy: opportunities and challenges

© 2023 The Authors. Published by American Chemical Society. This is an open access article under the Creative Commons Attribution-NonCommercial-NoDerivatives CC BY-NC-ND licence, https://creativecommons.org/licenses/by-nc-nd/4.0To provide precise medical regimens, photonics technologies have been involved in the field of nanomedicine. Phototriggered liposomes have been cast as promising nanosystems that achieve controlled release of payloads in several pathological conditions such as cancer, autoimmune, and infectious diseases. In contrast to the conventional liposomes, this photoresponsive element greatly improves therapeutic efficacy and reduces the adverse effects of gene/drug therapy during treatment. Recently, cancer immunotherpay has been one of the hot topics in the field of oncology due to the great success and therapeutic benefits that were well-recognized by the patients. However, several side effects have been encountered due to the unmonitored augmentation of the immune system. This Review highlights the most recent advancements in the development of photoresponsive liposome nanosystems in the field of oncology, with a specific emphasis on challenges and opportunities in the field of cancer immunotherapy.Peer reviewe

Iron oxide nanoflowers encapsulated in thermosensitive fluorescent liposomes for hyperthermia treatment of lung adenocarcinoma

Magnetic hyperthermia (MHT) is in the spotlight of nanomedical research for the treatment of cancer employing magnetic iron oxide nanoparticles and their intrinsic capability for heat dissipation under an alternating magnetic field (AMF). Herein we focus on the synthesis of iron oxide nanoflowers (Nfs) of different sizes (15 and 35 nm) and coatings (bare, citrate, and Rhodamine B) while comparing their physicochemical and magnetothermal properties. We encapsulated colloidally stable citrate coated Nfs, of both sizes, in thermosensitive liposomes via extrusion, and RhB was loaded in the lipid bilayer. All formulations proved hemocompatible and cytocompatible. We found that 35 nm Nfs, at lower concentrations than 15 nm Nfs, served better as nanoheaters for magnetic hyperthermia applications. In vitro, magnetic hyperthermia results showed promising therapeutic and imaging potential for RhB loaded magnetoliposomes containing 35 nm Nfs against LLC and CULA cell lines of lung adenocarcinoma

Recommendations for In Vitro and In Vivo Testing of Magnetic Nanoparticle Hyperthermia Combined with Radiation Therapy

Magnetic nanoparticle (MNP)-mediated hyperthermia (MH) coupled with radiation therapy (RT) is a novel approach that has the potential to overcome various practical difficulties encountered in cancer treatment. In this work, we present recommendations for the in vitro and in vivo testing and application of the two treatment techniques. These recommendations were developed by the members of Working Group 3 of COST Action TD 1402: Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therapy (“Radiomag”). The purpose of the recommendations is not to provide definitive answers and directions but, rather, to outline those tests and considerations that a researcher must address in order to perform in vitro and in vivo studies. The recommendations are divided into 5 parts: (a) in vitro evaluation of MNPs; (b) in vitro evaluation of MNP-cell interactions; (c) in vivo evaluation of the MNPs; (d) MH combined with RT; and (e) pharmacokinetic studies of MNPs. Synthesis and characterization of the MNPs, as well as RT protocols, are beyond the scope of this wor

A Novel Epigenetic Strategy to Concurrently Block Immune Checkpoints PD-1/PD-L1 and CD155/TIGIT in Hepatocellular Carcinoma

© 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the Creative Commons Attribution-Non Commercial-No Derivatives CC BY-NC-ND licence, https://creativecommons.org/licenses/by-nc-nd/4.0/Tumor microenvironment is an intricate web of stromal and immune cells creating an immune suppressive cordon around the tumor. In hepatocellular carcinoma (HCC), Tumor microenvironment is a formidable barrier towards novel immune therapeutic approaches recently evading the oncology field. In this study, the main aim was to identify the intricate immune evasion tactics mediated by HCC cells and to study the epigenetic modulation of the immune checkpoints; Programmed death-1 (PD-1)/ Programmed death-Ligand 1 (PD-L1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT)/Cluster of Differentiation 155 (CD155) at the tumor-immune synapse. Thus, liver tissues, PBMCs and sera were collected from Hepatitis C Virus (HCV), HCC as well as healthy individuals. Screening was performed to PD-L1/PD-1 and CD155/TIGIT axes in HCC patients. PDL1, CD155, PD-1 and TIGIT were found to be significantly upregulated in liver tissues and peripheral blood mononuclear cells (PBMCs) of HCC patients. An array of long non-coding RNAs (lncRNAs) and microRNAs validated to regulate such immune checkpoints were screened. The lncRNAs; CCAT-1, H19, and MALAT-1 were all significantly upregulated in the sera, PBMCs, and tissues of HCC patients as compared to HCV patients and healthy controls. However, miR-944–5p, miR-105–5p, miR-486–5p, miR-506–5p, and miR-30a-5p were downregulated in the sera and liver tissues of HCC patients. On the tumor cell side, knocking down of lncRNAs—CCAT-1, MALAT-1, or H19—markedly repressed the co-expression of PD-L1 and CD155 and accordingly induced the cytotoxicity of co-cultured primary immune cells. On the immune side, ectopic expression of the under-expressed microRNAs; miR-486–5p, miR-506–5p, and miR-30a-5p significantly decreased the transcript levels of PD-1 in PBMCs with no effect on TIGIT. On the other hand, ectopic expression of miR-944–5p and miR-105–5p in PBMCs dramatically reduced the co-expression of PD-1 and TIGIT. Finally, all studied miRNAs enhanced the cytotoxic effects of PBMCs against Huh7 cells. However, miR-105–5p showed the highest augmentation for PBMCs cytotoxicity against HCC cells. In conclusion, this study highlights a novel co-targeting strategy using miR-105–5p mimics, MALAT-1, CCAT-1 and H19 siRNAs to efficiently hampers the immune checkpoints; PD-L1/PD-1 and CD155/TIGIT immune evasion properties in HCC.Peer reviewe

Radiolabeled iron oxide nanoparticles functionalized with PSMA/BN ligands for dual-targeting of prostate cancer

IntroductionProstate cancer (PCa) is the second most frequent cancer diagnosis in men and the fifth leading cause of death worldwide. Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) receptors are overexpressed in PCa. In this study, we have developed iron oxide nanoparticles (IONs) functionalized with the Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) ligands for dual targeting of Prostate cancer.MethodsIONs were developed with a thin silica layer on their surface with MPTES (carrying -SH groups, IONs-SH), and they were coupled either with a pharmacophore targeting PSMA (IONs-PSMA) or with bombesin peptide (IONs-BN), targeting GRP receptors, or with both (IONs-PSMA/BN). The functionalized IONs were characterized for their size, zeta potential, and efficiency of functionalization using dynamic light scattering (DLS) and Fourier-Transform Infrared Spectroscopy (FT-IR). All the aforementioned types of IONs were radiolabeled directly with Technetium-99m (99mTc) and evaluated for their radiolabeling efficiency, stability, and binding ability on two different PCa cell lines (PC3 and LNCaP).Results and DiscussionThe MTT assay demonstrated low toxicity of the IONs against PC3 and LNCaP cells, while the performed wound-healing assay further proved that these nanostructures did not affect cellular growth mechanisms. The observed hemolysis ratio after co-incubation with red blood cells was extremely low. Furthermore, the 99mTc-radiolabeled IONs showed good stability in human serum, DTPA, and histidine, and high specific binding rates in cancer cells, supporting their future utilization as potential diagnostic tools for PCa with Single Photon Emission Computed Tomography (SPECT) imaging

Whither Magnetic Hyperthermia? A Tentative Roadmap

The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia.This work was supported by the NoCanTher project, which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 685795. The authors acknowledge support from the COST Association through the COST actions "RADIOMAG" (TD1402) and "MyWAVE" (CA17115). D.O., A.S.-O. and I.R.-R. acknowledge financial support from the Community of Madrid under Contracts No. PEJD-2017-PRE/IND-3663 and PEJ-2018-AI/IND-11069, from the Spanish Ministry of Science through the Ramon y Cajal grant RYC2018-025253-I and Research Networks RED2018-102626-T, as well as the Ministry of Economy and Competitiveness through the grants MAT2017-85617-R, MAT2017-88148R and the "Severo Ochoa" Program for Centers of Excellence in R&D (SEV-2016-0686). M.B. and N.T.K.T. would like to thank EPSRC for funding (grant EP/K038656/1 and EP/M015157/1) and AOARD (FA2386-171-4042) award. This work was additionally supported by the EMPIR program co-financed by the Participating States and from the European Union's Horizon 2020 research and innovation program, grant no. 16NRM04 "MagNaStand". The work was further supported by the DFG grant CRC "Matrix in Vision" (SFB 1340/1 2018, no 372486779, project A02)

New approach in synthesis, characterization and release study of pH-sensitive polymeric micelles, based on PLA-Lys-b-PEGm, conjugated with doxorubicin

Amphiphilic block copolymers are well established as building blocks for the preparation of micellar drug carriers. The functional polymer micelles possess several advantages, such as high drug efficiency, targeted delivery, and minimized cytotoxicity. The synthesis of block copolymers using nanostructured templates has emerged as a useful and versatile approach for preparing drug carriers. Here, we report the synthesis of a smart polymeric compound of a diblock PLA-Lys-b-PEG copolymer containing doxorubicin. We have synthesized functionalized diblock copolymers, with lysinol, poly(lactide) and monomethoxy poly(ethylene glycol) via thermal ringopening polymerization and a subsequent six-step substitution reaction. A variety of spectroscopic methods were employed here to verify the product of our synthesis. 1H-Nuclear magnetic resonance and Fourier transform infrared studies validated the expected synthesis of copolymers. Doxorubicin is chemically loaded into micelles, and the ex vitro release can be evaluated either in weak acidic or in SBF solution by UV–vis spectroscopy. Dynamic light scattering, thermo gravimetric analysis, and size exclusion chromatography have also been used

Synthesis and characterization complexes with medicinal chemistry interesting

The mononuclear copper complexes with the quinolones antibacterial drugs Enrofloxacin (erx) and Sparfloxacin (sf) in the presence or not of a nitrogen donor heterocyclic ligand 1,10-phenanthroline (=phen), 2,2’-bipyridine (=bipy) and bipyridilamine(=bipyam) have been prepared and characterized. Interaction of metallic anion with deprotonated ligamds leads to the formation of the neutral complex M(L)2(H2O)2, while the presence of phen or bipy, bipyam leads to the formation of a neutral complex respectively. The study of the interaction of the complexes with calf-thymus DNA has been performed with diverse spectroscopic techniques and has showed that all complexes are bound to DNA by intercalative mode. The antimicrobial efficiency of the complexes has been tested on three different microorganisms, Escherichia coli, Pseudomonas aeruginosa (Gram(-)) and St.Aureus (Gram(+)). The complexes also have been tested by cytotoxicity in two cell lines. The neutral mononuclear copper(II) complex with the quinolone antibacterial drug sparfloxacin has been prepared and characterized with IR, UV-vis, and EPR spectroscopies and X-ray crystallography. The interaction of the complex with calf-thymus DNA has also been investigated and the antimicrobial activity has been also evaluated against three different microorganisms. The neutral mononuclear vanadyl complex with the quinolone antibacterial drug enrofloxacin has been prepared and characterized with physicochemical and spectroscopic techniques and molecular mechanics calculations. The interaction of the complex with calf-thymus DNA has also been investigated and the antimicrobial activity has been evaluated against three different microorganisms. Seven novel metal complexes of the second-generation quinolone antibacterial agent enrofloxacin with Mn2+, Fe3+, Co2+, Ni2+, Zn2+, Cd2+ and UO22+ have been prepared and characterized with physicochemical and spectroscopic techniques. In these complexes, enrofloxacin acts as a bidentate deprotonated ligand bound to the metal through the pyridone and one carboxylate oxygen atoms. The central metal atoms are six-coordinate with slightly distorted octahedral geometry. Molecular modeling calculations have been performed in order to propose a model for the structure of Mn2+, Fe3+ and UO22+ complexes. The investigation of the interaction of the complexes with calf-thymus DNA has been performed with diverse spectroscopic techniques. The antimicrobial activity of the complexes has been tested on three different microorganisms. The complexes exhibit better or equal inhibition in comparison to free enrofloxacin. Three novel neutral mononuclear copper(II) complexes of the third-generation quinolone antibacterial drug sparfloxacin in the presence of a nitrogen donor heterocyclic ligand 2,2’-bipyridine, 1,10-phenanthroline or 2,2’-dipyridylamine have been prepared and characterized physicochemically and spectroscopically. The resultant complexes are of the type Cu(sparfloxacinato)(N-donor)Cl. Copper(II) is pentacoordinate having a distorted square pyramidal geometry. Molecular modeling calculations have been performed in order to propose the lowest energy model structure of the complexes. The interaction of the complexes with calf-thymus DNA has been investigated with diverse spectroscopic techniques and has shown that the complexes can bind to calf-thymus DNA by the intercalative mode. The antimicrobial activity of the complexes has been tested on three different microorganisms. ..................................................................Η αλληλεπίδραση μεταλλικών ιόντων με φάρμακα ή με ενώσεις γενικότερα που χρησιμοποιούνται σε κλινικές εφαρμογές παρουσιάζει έντονο και όλο και αυξανόμενο ενδιαφέρον. Οι κινολόνες είναι μία κατηγορία συνθετικών φαρμάκων, τα οποία είναι παράγωγα της 4-κινολόνης, και είναι γνωστά για την αντιβακτηριακή τους δράση κυρίως λόγω της παρεμπόδισης σχηματισμού του δεοξυριβονουκλεϊκού οξέος. Βασικοί εκπρόσωποι των κινολονών τα Enrofloxacin (erx), με ένα άτομο φθορίου στο μόριο, και το Sparfloxacin (Sf) το οποίο δεν περιέχει άτομο φθορίου στο μόριο, και Sparfloxacin το οποίο περιέχει δύο άτομα φθορίου στο μόριό του. Η παρούσα διατριβή αναφέρεται στο σχεδιασμό, τη σύνθεση, τη μελέτη και ο χαρακτηρισμός συμπλόκων ενώσεων των κινολονών και των με μεταλλικά ιόντα κυρίως των στοιχείων μετάπτωσης, με στοιχειακή ανάλυση και διάφορες φασματοσκοπικές μεθόδους (ΙR, UV-Vis, EPR). Παρασκευάστηκαν επίσης, σύμπλοκες ενώσεις των κινολονών με μεταλλικά ιόντα παρουσία υποκαταστατών ετεροκυκλικών ατόμων δοτών αζώτου, ενώσεων με βιολογική δραστικότητα, όπως 2,2-δυπιριδίνης, 1,10-Φαινανθρολίνης και 2,2’-δυπιριδιλαμίνης. Ακολούθησε η επίλυση της δομής με περίθλαση ακτίνων-Χ. Μελετήθηκε επίσης ο τρόπος της αλληλεπίδρασης αυτών των συμπλόκων με το DNA καθώς και η δράση τους απέναντι σε τρεις διαφορετικούς μικροοργανισμούς, E. Coli, Ps. Aeruginosa και St. Aureus. Πραγματοποιήθηκε προσδιορισμός της κυτταροτοξικής δράσης, τα πειράματα προσδιορισμού έδειξαν για τα σύμπλοκα απόπτωσης και προσδιορίστηκαν τα ποσοστά απόπτωσης σε σχέση, με τα νεκρωτικά κύτταρα, με κυτταρομετρία ροής. Στη συνέχεια ακολούθησε η σύνθεση αναλόγων της ταξόλης, της κολχικίνης και της θυροξίνης τα οποία συμπλέχθηκαν καν με συμπλοκες ενώσεις του συμπλέχθηκαν περαιτέρω με το γαδολίνιο, με σκοπό τη χρήση τους ως σκιαγραφικούς παράγοντες στη μαγνητική τομογραφία. Μετά την ολοκλήρωση της σύνθεσης και του χαρακτηρισμού, ακολούθησε η μελέτη των μαγνητικών ιδιοτήτων τους, προσδιορίστηκε η χαλάρωση (r) και μελετήθηκε η κυτταροτοξική δράση τους δράση